Method of protecting the skin from ultraviolet radiation



ron United States Patent Ofiice 3,030,275 Patented Apr. 17, 1962 Company, Inc, Believiiie, Ni, a corporation of New Jersey No Drawing. Filed Mar. '50, 1959, Ser. No. 302,663 2 Ciaims. (Cl. 167%) The present invention is directed to compositions for topical application, .and more particularly to those applicable as sun-screening agents against ultra-violet rays.

The use of sun-screening compounds in sun protective preparations is well understood. The function of the sun screen is to absorb practically all of the erythematogenie radiation found in sunlight before it strikes the skin of the user. This erythematogenic radiation is a portion of the electromagnetic radiation of the sun, and extends, in the ultraviolet range from wave lengths of approximately 290 millimicrons to a wavelength of approximately 320 millimicrons. Ultraviolet radiation of Wavelenght shorter than 290 millimicrons is absorbed by the earths atmosphere and does not reach the surface of the earth in suificient quantity to have an erythematogenie effect. Wavelengths above 320 millimicrons do not have an appreciable erythematogenic effect, and hence need not be screened from the human skin in order to prevent painful sunburn. On the contrary these higher wavelengths result in melanin formation leading to a desirably tanned skin.

It has long been known that trans-stilbene (trans-1,2- diphenylethylene) is a very effective sun-screening compound in the desired erythematogenic range. It has been found, however, that trans-stilbcne is readily and rapidly converted by ultraviolet irradiation to the cis-stilbene isomer, which is not a good absorber of the erythematogenie radiation. This ready interconversion of the transstilbene to the cis-stilbene renders the former material unsuitable for use in cosmetic sun screen preparations. According to spectrophotometric measurement of the extinction coefiicient of trans-stilbene, 2 percent of this material in a solution or lotion should be a sufficient concentration to afford protection to the average human skin against the development of a painful erythema. However, this observation is not substantiated by actual use tests. Thus, when a lotion containing 2 percent by weight of trans-stilbcne is placed on the skin, and the skin is exposed to the ultraviolet radiation of midday, midsummer sunlight for four hours, a painful sunburn results.

The present invention is intended and adapted to overcome the deficiencies of prior preparations of the type described, it being among the objects thereof to produce a series of eitective sun-screening compounds which are derivatives of trans-stilhene.

It is also among the objects of the invention to so design the structure of the compounds that the effective trans-isomers of the stilbene derivatives shall be stable to ultraviolet irradiation and shall not be converted to the ineffective cis configurations.

it is a further object of the invention to prepare such derivatives which will not, on exposure to light and air,

discolor or form other products which will discolor the person or the clothing of-the users.

In practicing the present invention it has been found that salts, esters and amides of 1,2-diphenylethylene-1- carboxylic acid are efficient absorbers'ot erythematogenic ultraviolet radiation, which are themselves stable to it'- radiation by ultraviolet irradiation, and which do not stain either the person or the clothing of the user, having the following structural formulae:

wherein Z is a member of a group consisting of 0X and NY and when Z is OX, X represents hydrogen, alkali metal, alkaline earth metal, and NH,, and when Z is NY Y represents hydrogen, alkyl groups having 1 to 8 carbon atoms, and hydroxyl alkyl groups wherein the alkyl groups have 2 to 3 carbon atoms.

Among the esters which are eifective are those in which the 1,2 -diphenylethylenel -carboxylic acid has been esterified by ethyl alcohol, isopropyl alcohol, isobutyl a1- cohol, methyl alcohol, glycols' or glycerol. The amides which are effective include the simple amide, and nitrogen-substituted amides. The free acid itself is also an effective and stable sun-screen.

For example, the spectrophotometric measurement of the extinction coefficient of ethyl-1,2-diphenylethylene-1- carboxylate indicates that a 3 percent concentration of this material in a solution or a lotion would be adequate to provide protection against painful erythema. This is substantiated by skin tests, for when a 3 percent (by weight) solution of the ethyl-1,2-diphenylethylenel-carboxylate is applied to normal human skin and the skin is exposed to the ultraviolet radiation of mid-day, mid-summer sunlight for four hours, no painful sunburn, and no perceptible erythema results. The same efficient protection is afforded by solutions of, for instance, the isobutyl ester, the methyl ester, the simple amide, the ammonium salt, the sodium salt and the potassium salt, as Well as by a solution of the free acid itself.

It is to be understood that the concentrations of choice of the sunscreens herein described are not limited to 3% solutions or lotions. Depending upon the normal response range of human skin to sunlight, and depending upon the amount of protection desired, the effective concentrations of the sunscreens may be varied over a relatively wide range. Thus, where less protection and more rapid tanning is desired, concentrations below 3% would be preferred, say .5% to 1.5%. Conversely, where tanning is not desired, or for use by humans extraordinarily sensitive to sunlight, concentrations above 3% would be preferred, even up to 6%8%.

The 1,2-diphenylethylene-l-carboxylic acid may be made in a variety of ways known to the art. For example, in a 200 cc. round bottomed flask, 17.4 g. (0.10 mole) of dry potassium phenylacetate, 5 g. of dry p0 tassium carbonate (0.035 mole), 0.5 cc. pyridine, 10.6 g. (0.10 mole) freshly distilled benzaldehyde, and 15.3 g. (0.15 mole) freshly distilled acetic anhydride are mixed thoroughly under nitrogen. An air-cooled reflux condenser is attached and the flask is carefully inserted in an oil bath at C. A vigorous bubbling takes place for a few minutes, after which the reaction proceeds quietly. Heating is continued at 180-190 C. for two hours. The mixture is allowed to cool, and 300-400 cc. water is added with gentle heating to break up lumps.

Potassium hydroxide solution (6 N) is added until the solution is basic (about 30 cc. is required), but care should be taken not to add a large excess of base as the potassium salt of the acid is easily salted out of solution. The mixture is heated until all soluble material has dissolved; sorne oily material Will remain undissolved. The flask is cooled under the water tap and the solution extracted with 300-400 cc. of ether to remove unchanged benzaldehyde and a little stilbene (ca. 1 g.). The water solution is acidified with 6 N hydrochloric acid (15-20 cc. is required), the precipitated acid filtered off, and the filtrate tested with more acid for completeness of precipitation. The precipitate is conveniently dried on a porous plate in a vacuum desiccator. The crude acid melts at about 160 C. It is recrystallized by dissolving in 50% ethanol at boiling temperature and adding Water until the solution is just cloudy. The solution is cooled very slowly, and long needles form gradually. The purified acid melts at 168l70 C. (uncor.). The acid obtained in this way is the trans-form.

The simple esters of the acid are prepared by direct esterification of the free acid by the appropriate alcohol in the presence of an acid catalyst, such as a minor amount of sulfuric or p-toluene sulfonic acid. These esters may then be purified by distillation under high vacuum. The salts are made simply by dissolving the acid in a stoichiometric quantity of the desired basic hydroxide or carbonate dissolved in a suitable quantity of water or other solvent. Upon evaporation of the solvent and concentration of the solution, the salt may be obtained in essentially pure form by crystallization. The amides may be prepared by heating the salt of the acid and the appropriate amine until one molecular equivalent amount of water is removed from the compound. The amide which is so formed may be purified by crystallization from an appropriate solvent. Another method is the treatment of the acid chloride with the desired amine to form the amide.

Those esters of mono-, di-, and tri-hydroxy alcohols having 1 to 4 carbon atoms are particularly satisfactory as Well as hydroxy alcohols, such as hydroxy ethyl and dihydroxy propyl obtained from ethylene glycol, glycerol and propylene glycol. For the amines used in making amides, the aliphatic amines, primary and secondary are preferable, the alkyl groups being preferably methyl, ethyl and normal and isopropyl and butyl. For alkanol amines, the monoand di-ethanol amines and mono-isopropanol amines are preferred.

Suitable formulations of carriers and sunscreen agents for the application of these sun-screens to the human skin can be prepared in a variety of Ways, depending upon the solubility characteristics of the particular derivative of the 1,2-diphenyl-1-carhoxylic acid which is employed. Thus, the ethyl and isobutyl esters may be dissolved in mineral oil and be applied to the skin in this clear, oily vehicle. The esters are also soluble in vegetable oils. The amides and the glycerol esters are not oil soluble, but are soluble in alcohol and hydro-alcoholic solution. The alcohols which may be used include the ethyl and isopropyl alcohols which are suitable for application to the skin. The salts of the acids are water soluble, alcohol soluble and hydro-alcohol soluble, and may be incorporated in clear lotions of these media. All of these derivatives, and the free acid may be dissolved in appropriate solvents and these solutions may be emulsified to form opaque emulsified lotions of the water-in-oil, or the oilin-water type. The emulsified lotions may either be of liquid consistency, or of the consistency of heavy pastes r creams. The lotions may be designed to be dispensed from glass bottles, plastic squeeze bottles, or from aerosol packages, using any convenient propellant. Similarly, the clear lotions may also be packaged in a variety of ways.

The following are specific examples of sun-screening compositions containing the present compounds:

EXAMPLE 1 Oily Suntan Lotion Parts by weight Color and perfume (sufficient to suit).

A; EAMPLE 2 Hydro-Alcoholic Suntan Lotion Parts by weight Ethyl alcohol SDA No. 40 47 Distilled water 47 Propylene glycol 3 1,2-diphenylethylene carboxylic acid 3 Color and perfume (sufficient to suit).

EXAMPLE 3 A composition according to Example 2 in which the sun-screcning agent is partly in the form of its sodium or potassium salt, or partly in the form of its glyceryl ester. Any one or any combination thereof may be substituted, in whole or in part for the free trans-stilbene carboxylic acid.

EXAMPLE 4 Emulsified Suntan Lotion The following compositions are provided:

Parts by weight Mineral oil, light 5.3 Stearic acid 6.1 Lanolin, anhydrous 2.1

Ethyl ester of 1,2-diphenylethylene-l-carhoxylic acid 3.0

The lotion is compounded according to the following procedure:

Heat the water and the sodium alginate to 70 C. Add the glycerine and the triethanolamine. Heat parts (A) and (C) separately to 70 C. While stirring (A), slowly add (C) and continue stirring until cooled to 50 C. Heat part (B) to 60 C. and add it slowly to the mixture of (A) and (C). Continue stirring until the lotion is cooled to 40 (3., add perfume and/or color as desired, and package.

The invention is not limited to those derivatives of the acid that are described herein, nor to the manner in which the acid or its derivatives are made, or to the manner in which the derivatives are formulated or dispensed. The essence thereof is the use of such substances in suntan lotions to provide long lasting protection afforded by the stability of said substances as set forth in the appended claims.

What is claimed is:

1. A method of protecting the human skin from the effects of exposure to ultraviolet radiation which comprises providing a cosmetic carrier, incorporating in said carrier a sunscreen agent having the formulawherein Z is a member of a group consisting of OX and NY and when Z is OX, X represents hydrogen, alkali metal, alkaline earth metal, and NH and when Z is NY Y represents hydrogen, alkyl groups having 1 to 8 carbon atoms, and hydroxy alkyl groups wherein the alkyl groups have 2 to 3 carbon atoms, and applying the above composition to the skin.

2. A method according to claim 1 characterized in that the amount of said agent in said composition is about .5 to 8%.

Chem. Abs., vol. 48, 1954, page 11307.

References Cited in the file of this patent UNITED STATES PATENTS Merkel Jan. 4, 1938 

1. A METHOD OF PROTECTING HUMAN SKIN FROM THE EFFECTS OF EXPOSSURE TO ULTRAVIOLET RADIATION WHICH COMPRISES PROVIDING A COSMETIC CARRIER, INCORPORATING IN SAID CARRIER A SINSCREEN AGENT HAVING THE FORMULA- 